Auspex Raises $25M for Longer-Lasting, Deuterium-Based Drugs
At San Diego’s Auspex Pharmaceuticals, CEO Larry Fritz is overseeing a drug development program based on a fairly simple premise: If an FDA-approved small molecule drug is susceptible to metabolic enzymes in the body that break down its hydrogen bonds, wouldn’t substituting some deuterium atoms make those bonds stronger and longer-lasting?
Deuterium is a stable and naturally occurring hydrogen isotope with a nucleus that is twice the mass of ordinary hydrogen. Fritz says replacing some hydrogen atoms with deuterium does not change the shape or electronic structure of a molecule. But as he put it in a recent phone call, “A few well-placed deuterium atoms can make a big difference.”
How big of a difference?
While the scientific basis for substituting deuterium has been generally established, Fritz says the pharmacokinetic effects have to be determined on a case-by-case basis.
Nevertheless, Auspex has enough confidence in the potential of its deuterium-based drug portfolio that the company has raised $25 million in a Series D round to help fund late-stage trials of its lead drug candidate. In a statement today, Auspex says the financing was led by Panorama Capital, and was joined by existing investors Thomas, McNerney & Partners, CMEA Capital, and Sloan Biotech Fund.
The company’s lead drug compound, SD-809, is a deuterium-based analog of tetrabenazine (Xenazine), a drug the FDA approved four years ago for treating the involuntary movements, or “chorea,” associated with Huntington’s disease, Tourette syndrome, and tardive dyskinesia.
Tetrabenazine is not a cure, but helps to control hyperkinetic movements by depleting dopamine, a neurotransmitter that, at abnormally high levels, causes chorea.
Replacing some of the 27 hydrogen atoms in tetrabenazine with deuterium makes it more difficult for metabolic enzymes to break the molecule down, Fritz says. “We can keep [SD-809] in the body longer because it doesn’t require as high doses or as many doses [as tetrabenazine]. There is a flatter pharamacokinetic curve and the interaction with other drugs is improved.”
While the Auspex drug poses similar side effects as tetrabenazine, which include restless pacing, depression, dizziness or drowsiness, and parkinsonism, Fritz says SD-809 should have therapeutic effects at lower doses. “Our hope is that because we won’t have to give those high doses that patients taking our drug will be able to stay within the therapeutic window.”
Although tetrabenazine was approved in the United Kingdom and Ireland in 1971, it took more than 20 years to get it into the drug pipeline in the United States. As USA Today’s Rita Rubin reported in 2008, pharmaceutical companies were reluctant to invest in U.S. clinical trials for a drug that targets Huntington’s disease. The reason? Huntington’s affects only about 30,000 Americans, and the estimated profit margin would be too small.
The size of the U.S. market could also prove to be a challenge for Auspex. Fritz says the company has raised about $59 million since the company was founded in 2001. The company’s current incarnation, however, began in 2007 when Thomas McNerney and CMEA first invested in the idea that deuterium’s “kinetic isotope effect” could have a broad effect in pharmaceuticals.
The company also has been applying its deuterium chemistry approach to SD-900, a compound for treating autoimmune diseases, and SD-560, a molecule for treating fibrotic diseases.